Opiate receptors solubilized with the zwitterionic detergent, CHAPS, behave as marcromolecular complexes carying at least two activities: reversible binding of opiate ligands, and a guanine nucleotide (and Na+) sensitive regulatory activity. In membranes prepared from neuroblastoma x glioma hybrid cell NG108-15 or rat striatum, opiate receptors inhibit adenylate cyclase activity by stimulatory GTP hydrolysis catalyzed by a specific, low Km, GTPase. These observations provide a general mechanism for the action of opiate receptors and for other inhibitory receptors coupled to adenylate cyclase.